Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice  

作　　者：Yong-sheng Zhou Hao-bo Tao Si-si Lv Ke-qin Liang Wen-yi Shi Ke-yi Liu Yun-yun Li Lv-yi Chen Ling Zhou Shi-jin Yin Qian-ru Zhao 

机构地区：[1]Department of Chemical Biology,School of Pharmaceutical Sciences,South-Central Minzu University,Wuhan,430074,China

出　　处：《Acta Pharmacologica Sinica》2024年第10期2045-2060,共16页中国药理学报（英文版）

基　　金：supported by National Natural Sciences Foundation of China(32000685);Knowledge Innovation Program of Wuhan-Shuguang Project(2022020801020412);Natural Sciences Foundation of Hubei Province(2020CFB348);Fundamental Research Funds for the Central Universities,South-Central Minzu University(CZQ23026)to QZ;partly by National Natural Sciences Foundation of China(81373379,81641186);National Key R and D Program of China(2019YFC1712402);Fundamental Research Funds for the Central Universities,South-Central Minzu University(CZZ19005)to SY.

摘　　要：Kv1.3 belongs to the voltage-gated potassium(Kv)channel family,which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders.Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals.Previous studies have explored the function of Kv1.3 in olfactory bulb,while the role of Kv1.3 in piriform cortex was less known.In this study,we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation,thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice.Coronal slices including the anterior piriform cortex were prepared,whole-cell recording and Ca^(2+)imaging of pyramidal neurons were conducted.We showed that the firing frequency evoked by depolarization pulses and Ca^(2+)influx evoked by high K^(+)solution were significantly increased in pyramidal neurons of Kv1.3 knockout(KO)mice compared to WT mice.Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCαwere activated in piriform cortex of Kv1.3 KO mice.Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression,proving that the presynaptic vesicle release might be elevated by Ca^(2+)influx.Using Golgi staining,we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice,supporting the stronger postsynaptic responses in these neurons.In olfactory recognition and feeding behavior tests,we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy)psoralen,a Kv1.3 channel blocker,in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice.In summary,Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex,which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

关 键 词：Kv1.3 piriform cortex neuronal excitability synaptic plasticity olfactory recognition 

分 类 号：R74[医药卫生—神经病学与精神病学]